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Genes 2015, 6(4), 935-956; doi:10.3390/genes6040935

Epigenetic Therapy for Solid Tumors: Highlighting the Impact of Tumor Hypoxia

1
Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, The University of Oxford, Oxford OX3 7DQ, UK
2
Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, KS 66160, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Jessica Tyler
Received: 30 June 2015 / Revised: 18 September 2015 / Accepted: 22 September 2015 / Published: 25 September 2015
(This article belongs to the Special Issue Chromatin Dynamics)
View Full-Text   |   Download PDF [768 KB, uploaded 25 September 2015]   |  

Abstract

In the last few decades, epigenetics has emerged as an exciting new field in development and disease, with a more recent focus towards cancer. Epigenetics has classically referred to heritable patterns of gene expression, primarily mediated through DNA methylation patterns. More recently, it has come to include the reversible chemical modification of histones and DNA that dictate gene expression patterns. Both the epigenetic up-regulation of oncogenes and downregulation of tumor suppressors have been shown to drive tumor development. Current clinical trials for cancer therapy include pharmacological inhibition of DNA methylation and histone deacetylation, with the aim of reversing these cancer-promoting epigenetic changes. However, the DNA methyltransferase and histone deacetylase inhibitors have met with less than promising results in the treatment of solid tumors. Regions of hypoxia are a common occurrence in solid tumors. Tumor hypoxia is associated with increased aggressiveness and therapy resistance, and importantly, hypoxic tumor cells have a distinct epigenetic profile. In this review, we provide a summary of the recent clinical trials using epigenetic drugs in solid tumors, discuss the hypoxia-induced epigenetic changes and highlight the importance of testing the epigenetic drugs for efficacy against the most aggressive hypoxic fraction of the tumor in future preclinical testing. View Full-Text
Keywords: DNA methylation; histone deacetylation; histone methylation; tumor hypoxia; gene-repression; epigenetic drugs DNA methylation; histone deacetylation; histone methylation; tumor hypoxia; gene-repression; epigenetic drugs
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Ramachandran, S.; Ient, J.; Göttgens, E.-L.; Krieg, A.J.; Hammond, E.M. Epigenetic Therapy for Solid Tumors: Highlighting the Impact of Tumor Hypoxia. Genes 2015, 6, 935-956.

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